Early antiplatelet therapy in coronary artery bypass grafting: a calculated benefit

Studies have demonstrated that antagonists of platelet activity, including aspirin and clopidogrel, reduce the risk of major adverse events in patients with acute coronary syndromes. Although antiplatelet agents also convey an increased risk of bleeding, particularly in patients proceeding to coronary artery bypass graft surgery, in most cases, the benefits of early initiation of antiplatelet therapy outweigh the risks. The purpose of this review is to distinguish perceived and actual risk versus the benefit associated with early antiplatelet therapy to help clinicians make informed decisions on using these agents in an acute setting where patients may require coronary artery bypass grafting.     

Antiplatelet therapy--Part I.

We summarize current information about aspirin and other antiplatelet drugs in patients with cardiac and vascular disease. For each indication, we briefly summarize the rationale for the use of antiplatelet therapy and describe the findings of relevant clinical trials. We propose recommendations for the use of these agents in clinical practice. Part I covers the use of antiplatelet therapy for the primary and secondary prevention of myocardial infarction, coronary thrombolysis, unstable and chronic stable angina, and coronary artery-saphenous vein bypass grafts. In part II we review the use of antiplatelet agents in coronary angioplasty, atrial fibrillation, artificial cardiac valves, stroke, and peripheral vascular disease.     

Platelet aggregation and antiplatelet agents in acute coronary syndromes

Antiplatelet agents are the cornerstone therapy of acute coronary syndromes. In the setting of ST elevation myocardial infarction, antiplatelet therapy prevent the prothrombotic effect of reperfusion therapy including thrombolysis and primary percutaneous coronary intervention. In non ST-elevation acute coronary syndromes, antiplatelet therapy prevent s complete coronary thrombotic occlusion and therefore the occurrence of ST elevation myocardial infarction. Antiplatelet agent benefit is related to the patient's risk profile. It is well established that combined antiplatelet therapy is the most effective in high risk patients. Several important issues have to be faced including the identification of non responders, dose adjustment and the management of temporary interruption of antiplatelet agents in stable coronary artery disease patients.     

Antiplatelet and anticoagulant therapy in elective percutaneous coronary intervention

Thrombosis plays a major role in acute vessel closure both after coronary balloon angioplasty and after stenting. This review will address the role of antiplatelet and anticoagulant therapy in preventing early thrombotic complications after percutaneous coronary intervention. The focus will be on agents that are routinely available and commonly used.     

Antiplatelet therapy--Part II.

We summarize current information about aspirin and other antiplatelet drugs in patients with cardiac and vascular disease. For each indication, we briefly summarize the rationale for the use of antiplatelet therapy and describe the findings of relevant clinical trials. We propose recommendations for the use of these agents in clinical practice. In Part 2, we discuss the use of antiplatelet agents in coronary angioplasty, atrial fibrillation, artificial cardiac valves, stroke, and peripheral vascular disease. In Part 1, we reviewed the use of antiplatelet therapy for the primary and secondary prevention of myocardial infarction, in conjunction with coronary thrombolysis, in patients with unstable and chronic stable angina, and following coronary artery-saphenous vein bypass grafting.     

In search of a better platelet ADP-receptor blocker

The second-generation antiplatelet agents – the inhibitors of the ADP receptor – have proven important in the management of acute coronary syndromes with or without coronary intervention.     

冠心病患者静息心率与血小板活性相关研究

目的:探讨冠心病患者静息心率与血小板活性的相关研究。方法:选择2013年1月至2014年9月于我院住院患者474例,按静息心率快慢分为三组,心率70 bmp为第一组(Q1)150例,心率位于70~85 bmp为第二组(Q2)265例,心率85 bmp为第三组(Q3)59例,三组患者均于病情稳定时行血栓弹力图(TEG)中MA值检测,同时随访3个月,观察和比较三组患者MA值变化及预后。结果:三组患者MA值分别为61.16±7.29 mm、62.02±7.46 mm、65.32±6.56 mm,第三组患者MA值与第一组或第二组患者MA值比较差异均存在统计学意义(P0.05),通过血栓弹力图检测三组经花生四烯酸(AA)途径的血小板抑制率和经二磷酸腺苷(ADP)途径的血小板抑制率发现,静息心率高低与抗血小板药物作用疗效无相关关系(P0.05)。随访3个月,三组患者心绞痛、再住院、脑血管病及死亡的总发生率分别为28%、28.68%、40.67%。结论:冠心病患者静息心率越快,MA值越大即血小板活性越高,静息心率的高低与抗血小板药物作用疗效无关。     

Anticoagulant and antiplatelet agents: their clinical and device application(s) together with usages to engineer surfaces

An essential aspect of the treatment of patients with cardiovascular disease is the use of anticoagulant and antiplatelet agents for the prevention of further ischaemic events and vascular death resulting from thrombosis. Aspirin and heparin have been the standard therapy for the management of such conditions to date. Recently, numerous more potent platelet inhibitors together with anticoagulant agents have been developed and tested in randomized clinical trials. This article reviews the current state of the art of antiplatelet and anticoagulant therapy in light of its potential clinical efficacy. It then focuses on the usages of these agents in order to improve the performance of clinical devices such as balloon catheters, coronary stents, and femoropopliteal bypass grafting and extra corporeal circuits for cardiopulmonary bypass. The article then goes on to look at the usage of these agents more specifically heparin, heparan, hirudin, and coumarin in the development of more biocompatible scaffolds for tissue engineering.     

Antithrombotic therapy

Coronary heart disease is the leading cause of death in the US and the industrialized world. Ever since DeWood in 1980 demonstrated that a thrombus was the primary event leading to acute myocardial infarction and that they may subsequently lyse, the mainstay of therapy for the past 25 years has been antithrombotic therapy aimed at coronary thrombosis. There have been numerous advances in the treatment of acute coronary syndrome with antiplatelet, antithrombotic, and fibrinolytic agents that have significantly reduced morbidity and mortality. The role of various pharmaceutical agents in the different phases of acute coronary syndrome is a complex and ever changing field.7.     

Plateletworks: a novel point of care platelet function screen

Platelet function is critically important in the acute-care settings of cardiopulmonary bypass surgery and percutaneous coronary intervention, which are commonly associated with the adverse vascular events of hemorrhage and thrombosis, respectively. To improve outcomes, it has been suggested that patients should be screened for platelet count and function periprocedurally, and therapeutic intervention including the possible use of thrombolytics and adequate anticoagulation or administration of antiplatelet agents, should be utilized. Antiplatelet therapy including aspirin (acetylsalicylic acid), the thienopyridines (clopidopgrel), and parenteral anti-glycoprotein (GP) IIb/IIIa agents (abciximab, tirofiban, and eptifibatide) are recognized as clinically important in patients at risk of developing thrombotic events. Recently, it has been recognized that empiric therapeutic administration of these agents may be suboptimal in clinical environments because of interpatient variability with regard to platelet count, platelet response, receptor concentration on the platelet, and other factors. Hence there is a clinical need to monitor such therapies on an individual basis. Traditional platelet tests including light transmission aggregometry (LTA) are inconvenient for acute diagnostic testing because of the complexity of the test and the requirement for specialty training. Hence, 'near-patient' test systems have recently been introduced. Plateletworks is an in vitro diagnostic, point-of-care test platform that has demonstrated utility in monitoring platelet response to all current antiplatelet agents including aspirin and clopidogrel.     

Optimal pharmacological therapy in ST-elevation myocardial infarction—a review

Antithrombotic therapy is an essential component in the optimisation of clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. There are currently several intravenous anticoagulant drugs available for primary percutaneous coronary intervention. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. However, these effective treatment strategies may be associated with bleeding complications. Compared with clopidogrel, prasugrel and ticagrelor are more potent and predictable, which translates into better clinical outcomes. Therefore, these agents are the first-line treatment in primary percutaneous coronary intervention. However, patients can still experience adverse ischaemic events, which might be in part attributed to alternative pathways triggering thrombosis. In this review, we provide a critical and updated review of currently available antithrombotic therapies used in patients with STEMI undergoing primary PCI. Finding a balance that minimises both thrombotic and bleeding risk is difficult, but crucial. Further randomised trials for this optimal balance are needed.     

In vitro platelet antiaggregatory properties of 4-methylcoumarins

Platelets play a crucial role in physiological haemostasis. However, in coronary arteries damaged by atherosclerosis, enhanced platelet aggregation, with subsequent thrombus formation, is a precipitating factor in acute myocardial infarction. Current therapeutic approaches are able to reduce approximately one quarter of cardiovascular events, but they are associated with an increased risk of bleeding and in some resistant patients are not efficient. Some coumarins possess antiplatelet activity and, due to their additional antioxidant effects, may be promising drugs for use in combination with the present therapeutic agents.     

Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

ABSTRACT: BACKGROUND: Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive.The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. METHODS: Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded. DISCUSSION: This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management.This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).     

Synthesis of new 5,6-dihydrobenzo[h]quinazoline 2,4-diamino substituted and antiplatelet/antiphlogistic activities evaluation

In pursuing our research on some 2,4-diamino-benzopyranopyrimidines and 2-amino-5,6-dihydrobenzo[h]quinazolines, previously reported as antiplatelet and analgesic/anti-inflammatory agents respectively, we designed and synthesized a new series of 5,6-dihydrobenzo[h]quinazoline 2,4-diamino substituted. The insertion of amino substituents at positions 2 and 4 of the benzoquinazoline scaffold resulted in compounds endowed with a potent ASA-like antiplatelet activity, combined with an anti-inflammatory activity comparable, in some cases, to that of indomethacin, used as a reference drug.     

Controversies and future perspectives of antiplatelet therapy in secondary stroke prevention

Antiplatelet agents are a cornerstone in the treatment of acute arterial thrombotic events and in the prevention of thrombus formation. However, existing antiplatelet agents (mainly aspirin, the combination of aspirin and dipyridamole and clopidogrel) reduce the risk of vascular events only by about one quarter compared with placebo. As a consequence, more efficacious antiplatelet therapies with a reduced bleeding risk are needed. We give an overview of several new antiplatelet agents that are currently investigated in secondary stroke prevention: adenosine 5′-diphosphonate receptor antagonists, cilostazol, sarpogrelate, terutroban and SCH 530348. There are unique features in secondary stroke prevention that have to be taken into account: ischaemic stroke is a heterogeneous disease caused by multiple aetiologies and the blood–brain barrier is disturbed after stroke which may result in a higher intracerebral bleeding risk. Several small randomized trials indicated that the combination of aspirin and clopidogrel might be superior to antiplatelet monotherapy in the acute and early post-ischaemic phase. There is an ongoing debate about antiplatelet resistance. Decreasing response to aspirin is correlated independently with an increased risk of cardiovascular events. However, there is still no evidence from randomized trials linking aspirin resistance and recurrent ischaemic events. Similarly, randomized trials have not demonstrated a clinical significantly decreased antiplatelet effect by the concomitant use of clopidogrel and proton pump inhibitors. Nevertheless, a routine use of this drug combination is not recommended.     

Synthesis, antiplatelet and antithrombotic activities of new 2-substituted benzopyrano[4,3-d]pyrimidin-4-cycloamines and 4-amino/cycloamino-benzopyrano[4,3-d]pyrimidin-5-ones

Atherothrombotic coronary artery disease, associated with deep vein thrombosis, is one of the most common causes of death worldwide. Recently, antiplatelet combination therapy using agents with different mechanisms of action, such as aspirin, dipyridamole, and thienopyridines, seems to be an attractive preventive approach. Moreover, several large, randomized clinical trials support combination therapy with aspirin plus warfarin in high-risk patients with atherosclerotic heart disease. Our research on the benzopyrano[4,3-d]pyrimidine system gave rise to the synthesis of a large number of compounds endowed with in vitro anti-aggregating activity. Several SAR considerations suggest that the benzopyranopyrimidine system is an appropriate scaffold to obtain molecules that are able to act simultaneously in different pathways of aggregation. Now, we report the synthesis of new 2-substituted benzopyrano[4,3-d]pyrimidin-4-cycloamines and 4-amino/cycloamino-benzopyrano[4,3-d]pyrimidin-5-ones and the results of the pharmacological study on haemostasis. Some tested compounds showed a large-spectrum antiplatelet activity in vitro, and are more potent than aspirin as antithrombotics in vivo but, at variance with aspirin, they do not increase bleeding. This paper describes novel antithrombotic compounds with an interesting pharmacological profile and a potentially attractive benefit/risk ratio, with their mechanism of action generally, but not exclusively, dependent on antiplatelet activity, deserving further investigations.     

阿司匹林、氯吡格雷及西洛他唑预防和治疗老年冠脉支架植入术后血小板高反应性的临床效果观察

目的:探讨阿司匹林、氯吡格雷及西洛他唑预防和治疗老年冠脉支架植入术后血小板高反应性的临床效果。方法:选择60例拟行冠脉支架植入术的老年患者,随机地分为加用或未加用200 mg西洛他唑负荷剂量组。术前、术后24小时及术后30天时检测和比较各组患者的血小板聚集功能。结果:三联抗血小板治疗组的PRU、ARU及P2Y12%inhibition值均较两联抗血小板治疗组显著降低,差异具有统计学意义(P0.05)。三联抗血小板治疗和两联负荷剂量的抗血小板治疗的给药时间(第一次投药至冠脉介入治疗的时间间隔)分别为10.2小时(95%可信区间:7.4-13.1小时)和7.8小时(95%可信区间:4.5-11.2小时),三联抗血小板治疗组术前HPPR(83.3%和46.7%,P=0.003)、术后24小时(36.7%和13.3%,P=0.018)及术后30天HPPR(40.0%和16.7%,P=0.045)的发生率均较两联抗血小板治疗组明显降低(P0.05)。在术后30天的随访观察期间,两联抗血小板治疗组2例患者出现支架内血栓,并进行了血运重建术;无1例心源性死亡、缺血性卒中及出血性并发症的发生。两组次要终点的发生率比较无显著性差异(P0.05)。结论:在两联抗血小板聚集治疗的基础上附加200 mg西洛他唑可显著降低冠状动脉支架植入术后血小板的高反应性。     

How cardiologists manage antithrombotic treatment of patients with atrial fibrillation undergoing percutaneous coronary stenting: the WOEST survey 2018

BackgroundAntithrombotic treatment choices are complicated when patients have both atrial fibrillation (AF) and acute coronary syndrome and/or undergo percutaneous coronary intervention (PCI). In this study, we aimed to gain insight into antithrombotic management strategies in daily clinical practice.MethodsWe invited interventional cardiologists to complete the WOEST (What is the Optimal antiplatElet & Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary StenTing) survey 2018. In this questionnaire, we presented a patient with a non-ST-elevation myocardial infarction (NSTEMI) and an elective PCI case.ResultsThe results were based on 118 completed questionnaires (response rate 69.4%). In the case of the AF patient with NSTEMI, most cardiologists indicated they would initiate dual antiplatelet therapy (acetylsalicylic acid and clopidogrel) and continue non-vitamin K antagonist oral anticoagulant (NOAC) therapy at admission and during coronary angiography/PCI. At discharge, 70.3% would prescribe triple antithrombotic therapy (oral anticoagulation, acetylsalicylic acid and clopidogrel), mostly for 1 month. One year after NSTEMI, 83.1% would cancel the antiplatelet therapy and prescribe NOAC monotherapy. For the AF patient undergoing elective PCI, 51.7% would start dual antiplatelet therapy prior to the procedure and 52.5% would discontinue NOAC therapy prior to the PCI. At discharge, 55.1% would start triple antithrombotic therapy. Furthermore, 25.4% responded they routinely prescribe a reduced dose of NOAC after discharge. One year after PCI, 89.0% would continue NOAC monotherapy.ConclusionThe WOEST survey demonstrated heterogeneity in antithrombotic management strategies among interventional cardiologists. This observed variety mirrors the heterogeneity of the many guidelines and consensus documents. Further research is needed to guide patient-tailored medicine for AF patients undergoing PCI.Electronic supplementary materialThe online version of this article (10.1007/s12471-020-01500-3) contains supplementary material, which is available to authorized users.     

The use of adjunctive GPIIb/IIIa inhibitors in patients with unstable angina/non-Q-wave MI undergoing percutaneous coronary intervention

Glycoprotein IIb/IIIa receptor inhibitors represent a relatively new therapeutic approach in the field of antiplatelet therapy. Following the development of abciximab a number of small molecule GPIIb/IIIa inhibitors have been introduced such as tirofiban and eptifibatide. In this fast-moving field the interventional cardiologist needs a framework to guide decision-making for the individual patient. This review covers the efficacy and safety data from the clinical trials of GPIIb/IIIa inhibitors in the context of patients undergoing percutaneous coronary intervention for unstable angina/non-Q-wave myocardial infarction. There is an increasing body of evidence to support the efficacy of GPIIb/IIIa inhibitors in reducing the risk of adverse ischemic events in high and low risk patients undergoing percutaneous coronary intervention. A number of unresolved efficacy and safety issues remain, including the duration of treatment before and after intervention; whether a reduction in the heparin dose would further decrease the risk of hemorrhage without affecting the periprocedural thrombotic rate in patients undergoing PTCA with adjunctive GPIIb/IIIa inhibitors; and the cost-effectiveness of this therapy. When a thorough analysis of cost-effectiveness has been made, it will be easier to advocate the widespread use of these agents in all patients undergoing coronary intervention.     

Platelet proteomics and its advanced application for research of blood stasis syndrome and activated blood circulation herbs of Chinese medicine

The development of novel and efficient antiplatelet agents that have few adverse effects and methods that improve antiplatelet resistance has long been the focus of international research on the prevention and treatment of cardiovascular and cerebrovascular diseases. Recent advances in platelet proteomics have provided a technology platform for high-quality research of platelet pathophysiology and the development of new antiplatelet drugs. The study of blood stasis syndrome (BSS) and activated blood circulation of traditional Chinese medicine (TCM) is one of the most active fields where the integration of TCM and western medicine in China has been successful. Activated blood circulation herbs (ABC herbs) of Chinese medicine are often used in the treatment of BSS. Most ABC herbs have antiplatelet and anti-atherosclerosis activity, but knowledge about their targets is lacking. Coronary heart disease (CHD), BSS, and platelet activation are closely related. By screening and identifying activated platelet proteins that are differentially expressed in BSS of CHD, platelet proteomics has helped researchers interpret the antiplatelet mechanism of action of ABC herbs and provided many potential biomarkers for BSS that could be used to evaluate the clinical curative effect of new antiplatelet drugs. In this article the progress of platelet proteomics and its advanced application for research of BSS and ABC herbs of Chinese medicine are reviewed.